| Demographic Data |
| Relation to Proband |
proband |
| Age at Sampling |
4 YR |
| Sex |
Female |
| Age of Onset(If not a control) |
18 MO |
| Age at Diagnosis(If not a control) |
2 YR |
| Racial Category |
Asiatic Indian |
| Country |
USA |
| |
| Data Elements |
| Clinical Element Type: General NIGMS Catalog Remarks |
| (Baseline) |
| Mutation Information |
| Gene, variant, consequence, and exon number: |
WHOLE EXOME SEQUENCING OF THIS INDIVIDUAL'S DNA IDENTIFIED PATHOGENIC/LIKELY PATHOGENIC AUTOSOMAL RECESSIVE COMPOUND HETEROZYGOUS VARIANTS IN THE SURF1 GENE (NM_003172.2): PATERNALLY INHERITED C.751C>T (P.Q251*) IN EXON 7 AND MATERNALLY INHERITED C.796DUPA (P.T266NFS*26) IN EXON 8; READS WERE ALIGNED TO HUMAN GENOME BUILD GRCH37/UCSC HG19 |
| Zygosity: |
Compound Heterozygous |
| Other variants: |
HAS A PATERNALLY INHERITED COPY NUMBER VARIANT CONFIRMED BY EXOME SEQUENCING: DUPLICATION AT 4Q35.1Q35.2; MITOCHONDRIAL SEQUENCE ANALYSIS AND DELETION TESTING OF THE MITOCHONDRIAL GENOME REVEALED THAT THIS INDIVIDUAL IS HOMOPLASMIC FOR A MATERNALLY INHERITED VARIANT OF UNKNOWN CLINICAL SIGNIFICANCE: M.8953A>G (P.ILE143VAL) |
| Age of Symptom Onset and Age at Diagnosis |
| Age of Symptom Onset: |
18 MONTHS |
| Age at Diagnosis: |
DIAGNOSED AT 2 YEARS OF AGE BY A GENETICIST |
| In Utero History Information |
| |
|
| Additional Information: |
BORN AT TERM; UNCOMPLICATED PREGNANCY; DEVELOPED BRADYCARDIA DURING DELIVERY |
| Birth History Information |
| |
Failure to thrive
Caesarian section
|
| Additional Information: |
EMERGENCY C-SECTION DUE TO BRADYCARDIA; DIFFICULTY GAINING WEIGHT AFTER 7 MONTHS OF AGE |
| Dysmorphic Features |
| |
|
| Additional Information: |
CONGENITAL BILATERAL PTOSIS - RESOLVED AT 2 YEARS; WEAK FACIAL MUSCLES |
| Neurological Symptoms |
| |
Ataxia
Hypotonia
|
| Additional Information: |
SEVERE HYPOTONIA WITH AXIAL SLIPPAGE; HYPERREFLEXIA |
| Optical and Audiological Symptoms |
| |
|
| Musculoskeletal Symptoms |
| |
|
| Developmental Milestones |
| |
Delayed gross motor skills
|
| Sitting Without Assistance: |
Achieved and maintained |
| Additional Information: |
DEVELOPMENT: SAT ALONE AT 6 MONTHS, PULLED TO STAND AT 7 MONTHS, CREEPED AT 8 MONTHS, 1ST WORDS AT 10 MONTHS; UNABLE TO WALK AT 19 MONTHS; CURRENT MOTOR SKILLS: SITS ALONE AND REACHES FOR OBJECTS, ABLE TO STAND AND CREEP BUT UNABLE TO STAND INDEPENDENTLY; APPROPRIATE LANGUAGE DEVELOPMENT; REGRESSION IN MOTOR SKILLS AT 2 YRS OF AGE, - INCREASED FALLS AND DECREASED ABILITY TO STAND AND CRUISE; ADVANCED LANGUAGE DEVELOPMENT; SPEECH IS DYSARTHRIC |
| Gastrointestinal Symptoms |
| |
Constipation
|
| Additional Information: |
LACTIC ACIDOSIS (56 MG/DL AT 20 MOTHS, REFERENCE IS 4-16) |
| Genitourinary Symptoms |
| |
|
| Respiratory and Cardiovascular Symptoms |
| |
|
| Additional Information: |
AT RISK TO DEVELOP RECURRENT NECROTIZING DEMYELINATION OF MIDLINE BRAIN STRUCTURES WITH ANY INFECTION |
| Cognitive and Behavioral Symptoms |
| |
|
| Additional Information |
| Testing Performed |
| Neurological Testing: |
LEIGH SYNDROME DIAGNOSED AFTER BRAIN MRI AT 25 MONTHS OF AGE |
| Respiratory and Cardiovascular Testing: |
NORMAL ECG; MRI SHOWED INVOLVEMENT OF BRAINSTEM, BILATERAL SYMMETRIC LESIONS TO THE BASAL GANGLIA AND PUTAMEN |
| Metabolic, Hematologic, and Endocrinologic Testing: |
AT 19 MONTHS OF AGE, CBC, ALT, AST, T4/TSH AND CREATININE WERE NORMAL; HISTORY OF LACTIC ACIDOSIS (56 MG/DL, REFERENCE IS 4-16); ELEVATED PYRUVATE IN URINE ORGANIC ACIDS TEST; ELEVATED ALANINE IN PLASMA AMINO ACIDS |
| Treatments and Assistive Devices |
| |
Occupational therapy
Physical therapy
Speech therapy
Wheelchair or ambulation devices
|
| Additional Testing: |
BRACES; SURGERY: G-TUBE |
| Medications |
| |
THIMINE, MVI (MULTIPLE VITAMINS INJECTION) |
| Family History |
| |
UNAFFECTED CARRIER MOTHER IS GM28014 (FIBRO); NO HISTORY OF CONSANGUINITY, PROBLEMS SIMILAR TO THAT OF SUBJECT, OR MENTAL RETARDATION, SEIZURES, MUSCLE WEAKNESS, VISUAL LOSS, HEARING LOSS, UNEXPLAINED DEATHS, SHORT STATURE, POOR WEIGHT GAIN, KIDNEY PROBLEMS, LIVER PROBLEMS, CONSTIPATION, LIVER FAILURE, CARDIOMYOPATHY, EARLY ONSET, STROKES, OR DIABETES; MOTHER HAD SINGLE 1ST TRIMESTER MISCARRIAGE; VARIANT SEGREGATION ANALYSIS BY WES REVEALED THAT THE MOTHER CARRIES THE C.796DUPA (P.T266NFSX26) VARIANT AND THE FATHER (NOT IN REPOSITORY) CARRIES THE C.751C>T(P.Q251X) VARIANT IN SURF1; MOTHER CARRIES THE MITOCHONDRIAL DNA VARIANT M.8953A>G (P.ILE143VAL); FATHER CARRIES THE COPY NUMBER VARIANT DUPLICATION AT 4Q35.1Q35.2 |
| Remarks |
See "Phenotypic Data" Tab; unaffected carrier mother is GM28014 (fibroblast). |